After The Deluge, Hep C Players Look For Opportunity

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Includes: ABBV, GILD, MRK
by: EP Vantage

Hepatitis C’s second wave has crested and crashed, and this gold rush looks like it will be succeeded by a new generation of more effective, if less lucrative agents.

Predictably, Gilead Sciences (NASDAQ:GILD) got there first in the race to launch a drug that covers all six genotypes of the viral infection, but others are coming quickly, with AbbVie’s (NYSE:ABBV) pan-genotype combination of glecaprevir and pibrentasvir looking about as effective with a shorter treatment course. These could be among the last of the broadly used hep C agents to be launched, as Gilead seems to have shifted to sicker patients with its upcoming triple combination.

AbbVie has failed to make the most of its relatively early entry into hep C, as its Viekira Pak did not live up to frothy expectations. Along with Gilead’s Sovaldi, Viekira offered patients the first treatment regimens that did not include interferon, which has demanding side effects. Sovaldi mostly won the day with its broader genotype coverage and once-daily single pill – in addition, Gilead followed up quickly with the ribavirin-free two-drug pill Harvoni.

The pan-genotype hepatitis C products

Product

Company

SVR12 (phase III)

Dosage

WW sales 2022e ($m)

Epclusa (sofosbuvir & velpatasvir)

Gilead

85%-100%

once daily, one tablet

2,580

Sofosbuvir, velpatasvir & voxilaprevir

Gilead

95%-97%

once daily, one tablet

859

Glecaprevir & pibrentasvir

AbbVie

95%-99%

once daily, three tablets

481

Consensus forecasts from EvaluatePharma

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Now AbbVie has an opportunity to make amends with the glecaprevir/pibrentasvir (ABT 493 & ABT 530) combination, which in recent days has announced positive data in trials crossing all six genotypes of hep C. Today, the Illinois-based company released late-breaking results from the Expedition-4 trial at the AASLD meeting. This study covered genotype 1-6 patients with chronic kidney disease and included patients on dialysis and with compensated cirrhosis.

Last week, AbbVie also announced results from studies in less sick patients. They found a 99% cure rate 12 weeks after treatment conclusion in treatment naïve and experienced genotype 1 patients, 97% in treatment naïve and experienced patients with genotypes 2, 4, 5 and 6, and 95% for treatment naïve genotype 3 patients. All these patients had no signs of cirrhosis.

An advantage AbbVie’s new entry could offer over Epclusa is its shorter, eight-week treatment regimen in less sick patients, although the Gilead agent can be used with ribavirin to treat cirrhotic patients and has one daily pill to AbbVie’s three.

AbbVie plans to submit the new combination to the FDA by the end of 2016 and to European authorities in early 2017.

In the scheme of hepatitis C, where Harvoni reached nearly $14bn in sales in its first full year on the market, the outlook for these new agents is pretty modest – Epclusa is set to peak at $3.4bn in sales in 2019 before falling back to $2.7bn by 2022, while AbbVie’s double combination will peak at $533m in 2020 before declining to $481m two years later, according to EvaluatePharma. Yet, despite the modest outlook, both Epclusa and glecaprevir/pibrentasvir will rank among the top 10 hep C drugs in 2022.

With so many patients in the wealthy Western nations already now having sought treatment with effective drugs largely free of side effects, the remaining hep C market will consist of the newly infected, harder-to-treat patients like those with genotype 3 or who have not been cured with existing drugs, and patients in developing nations.

Here come the triplets

One-time excitement about triple combinations has died away with the huge success of the incumbents, and it is looking more like these will offer incremental improvements in treatment rather than the transformative advances of Sovaldi and Harvoni.

Gilead has signalled that it is aiming its triplet, sofosbuvir, velpatasvir and voxilaprevir at the salvage and cirrhotic genotype 3 population in spite of its rather broad effectiveness. Merck & Co. (NYSE:MRK) has likewise done the same with its combination of Zepatier plus MK-3682, now in phase II.

The Gilead triplet is reckoned to sell $859m in 2022, and may have the distinction of being the only hepatitis C drug without a peak sales forecast in the next five years. That may be cold comfort for Gilead after the huge success of Sovaldi and Harvoni.

Chief executive John Milligan recently acknowledged that the triplet will be its last hep C product because “there really isn't much left in terms of unmet medical need.” Realism seems to have set in at Gilead’s California headquarters – the future of hep C looks relatively modest.